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Hua J Kern, Susan Hazels Mitmesser The Nature’s Bounty Co., Ronkonkoma, NY, USA Abstract: Metabolic syndrome (MetS) and its associated chronic disorders including cardiovascular disease and type 2 diabetes are public health concerns in the USA and worldwide. “Good health is an investment in economic growth,” and nutrition is one of the recommended preventive measures to manage these chronic diseases. However, it is unclear whether and to what extent nutrients could be beneficial to the improvement of MetS. To help answer this question, we performed a literature review of the emerging human data on single nutrients and MetS: PubMed was searched from January 1, 2005 to June 12, 2017, using a combination of the following keywords: “nutrient” OR “vitamin” OR “mineral” OR “nutraceutical” AND “metabolic syndrome.” The summary of literature comprises macronutrients (proteins/amino acids, fatty acids, fibers, and sugar), micronutrients (antioxidant vitamins, vitamin D, folate, magnesium, and chromium), polyphenols (flavonoids, resveratrol, isoflavones, and chlorogenic acid), and other compounds (α-lipoic acid, benfotiamine, fucoxanthin, policosanol, and stanols). Bearing a holistic approach in mind, we also highlighted select lifestyle factors that may contribute to MetS (such as circadian rhythm and nutrition in early life). Observational studies have generated positive evidence supporting the beneficial role of numerous nutrients in MetS. Although the results of some clinical trials are consistent with the observational data, causality is not always clear or consistent across trials. Both nutrition and health are complex and dynamic systems with a hierarchical nature. When we design confirmatory trials to investigate nutrient(s) and MetS, instead of the traditional “single-nutrient” concept, it is worth considering a holistic approach to integrate groups or classes of nutrients, lifestyle influencers (ie, diet and physical activity), and population relevance (ie, healthy, at-risk, or diseased). Keywords: nutrient, metabolic syndrome, obesity, hypertension, dyslipidemia, insulin resistance

Pediatricians typically use Centers for Disease Control and Prevention 2000 growth charts as reference tools to monitor and assess infant health and nutritional status. The World Health Organization 2006 growth charts, defined as a global growth standard, have been proposed for this use. To date, there are no longitudinal, prospective published data analyses for US and Canadian infants to evaluate the impact of adopting the World Health Organization charts. Because interventions are often driven by interpretation of weight percentiles, healthcare professionals need to be aware that the adoption of the World Health Organization 2006 growth charts may result in differences in infant weight categorization. The World Health Organization 2006 growth charts also include a body mass index chart for infants. Body mass index provides a reference used worldwide for classifying weight status in the older child and adult. However, it is not clear whether the body mass index chart is an appropriate screening tool to define infants younger than 2 years at risk for overweight and/or obesity. [ABSTRACT FROM AUTHOR]

To assess the effect of docosahexaenoic acid and arachidonic acid supplementation in infant formula on the incidence of respiratory illnesses, pediatricians assigned infants to receive docosahexaenoic acid/arachinonic acid-supplemented formula or control formula. Anthropometrics, medical history, and illnesses were reported. Among 1342 infants, there was a higher incidence of bronchiolitis in control versus docosahexaenoic acid/arachinonic acid-supplemented groups at 5, 7, and 9 months (P < .01). Weight, length, and head circumference were similar for both groups. Infants fed formula supplemented with 0.32% docosahexaenoic acid and 0.64% arachidonic acid experienced a lower incidence of bronchiolitis compared with infants fed formula supplemented with no docosahexaenoic acid/arachidonic acid or lower levels of docosahexaenoic acid/arachidonic acid in the first year of life. [ABSTRACT FROM AUTHOR]

Exogenous melatonin can be helpful for treatment of some sleep disorders. However, immediate-release formulations are rapidly absorbed and cleared from the body making it difficult to provide coverage for an entire sleep period. Extended-release melatonin formulations can better mimic the naturally occurring melatonin profile and increase efficacy, but few studies have reported on their pharmacokinetics. To assess the pharmacokinetics of extended-release melatonin, we conducted a randomized, double-blind, crossover study of extended-release melatonin (4 mg) compared to immediate-release melatonin (4 mg) in 18 healthy adults, ages 18-65 years. Participants received immediate-release or extended-release melatonin in clinic after an 8 h fast, and blood samples were taken over a 10-h period. After a 7-day washout period, the same procedures were repeated with the melatonin form not previously received. Extended-release melatonin had a longer time to peak concentration (1.56 vs 0.6 h) and elimination half-life (1.63 vs 0.95 h) compared with immediate-release melatonin. Maximum concentration was lower for extended-release melatonin compared with immediate-release melatonin (7581 pg/mL vs 13120 pg/mL). Extended-release melatonin raised melatonin levels in as little as 15 min and sustained elevated melatonin levels (>300 pg/mL) for 6 h before falling below 50 pg/mL by 9 h. No clinically relevant adverse events were observed, and safety parameters remained within normal ranges for both formulations. The pharmacokinetic profile of this extended-release melatonin formulation suggests that it could be used for future efficacy studies of melatonin and sleep outcomes. This trial is registered at ClinicalTrials.gov, NCT04067791.

The Patient Protection and Affordable Care Act, more commonly known as the ACA, was legislation passed in the United States in 2010 to expand access to health insurance coverage for millions of Americans with a key emphasis on preventive care. Nutrition plays a critical role in overall wellness, disease prevention and resilience to chronic illness but prior to the ACA many Americans did not have adequate health insurance coverage to ensure proper nutrition. With passage of the ACA, more individuals received access to nutritional counseling through their primary care physicians as well as prescription vitamins and supplements free of charge. The objective of this study was to evaluate the impact of a national health insurance reform on nutrient intake among general population, including more vulnerable low-income individuals and patients with chronic conditions. Using data from the National Health and Nutrition Examination Survey (NHANES), we identified 8,443 adults aged 21 years and older who participated in the survey before (2011-2012) and after the ACA (2015-2016) implementation and conducted a subgroup analysis of 952 respondents who identified as Medicaid beneficiaries and 719 patients with a history of cancer. Using pre-post study design and bivariate and multivariable logistic analyses, we compared nutrient intake from food and supplementation before and after the ACA and identified risk factors for inadequate intake. Our results suggest that intake of micronutrients found in nutrient-dense foods, mainly fruit and vegetables, has not changed significantly after the ACA. However, overall use of nutritional supplements increased after the ACA ( p = 0.05), particularly magnesium (OR = 1.02), potassium (OR = 0.76), vitamin D (both D2, and D3, OR = 1.34), vitamin K (OR = 1.15) and zinc (OR = 0.83), for the general population as well as those in our subgroup analysis Cancer Survivors and Medicaid Recipients. Given the association of increased use of nutritional supplements and expansion of insurance access, particularly in our subgroup analysis, more research is necessary to understand the effect of increasing access to nutritional supplements on the overall intake of micro- and macronutrients to meet daily nutritional recommended allowances., Competing Interests: PD, KM, and SM were employed by Pharmavite. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kirk, Tufuor, Shaver, Nie, Devarshi, Marshall, Mitmesser and Noyes.)

Background: An increasing number of adults are over the age of 65, and there is concern about the increasing prevalence of age-associated cognitive decline and poor mental health status in older adults in the United States. Several nutrients are known to have important biological roles in brain health and neurological function, but many individuals fall short of recommended intake levels. The objective of this study was to examine the association between nutrient intake and cognitive function. We also explored whether nutrient intake was associated with depression., Methods: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and included participants ≥ 60 years of age who had reliable day 1 dietary recall data and either valid cognitive function data (n = 2713) or valid depression score data (n = 2943). The sample was stratified by gender, and cognitive functioning test (CFT) composite z-scores were analyzed by quartiles. Depression status was assessed using the Patient Health Questionnaire (PHQ-9)., Results: Higher intake and adequacy of a number of different nutrients from food were associated with higher cognitive function in both males and females. Nutrients that showed the most consistent associations with cognitive function across intake and adequacy analyses for food in both males and females were vitamin A, vitamin E, thiamin, riboflavin, vitamin B6, folate, magnesium, potassium, zinc, vitamin K, and lutein and zeaxanthin (p < 0.05 for all). These associations were positive with increasing intake and adequacy being associated with higher CFT composite z-scores. Analysis of nutrient intake and depression yielded results that differed by gender. In females, the nutrients that showed consistent inverse associations with depression scores across both intake and adequacy analyses for food were vitamin A, vitamin C, magnesium, vitamin K, potassium, and dietary fiber (p < 0.05 for all). In males, no significant associations between nutrient intake from food and depression scores were observed., Conclusions: Our findings suggest that older adults with sufficient intakes of certain essential nutrients have higher cognitive function. Future studies are needed to confirm whether a well-balanced diet and/or dietary supplements which emphasize these nutrients are effective for prevention of age-related declines in cognitive function and mood., (© 2023. The Author(s).)

The influence of individual macro- and micronutrients on absenteeism in the United States is largely unknown. The objective of this study was to determine whether nutritional status or nutrient intake were associated with absenteeism from school and work due to illness or injury. Data from NHANES 2003-2008 were used to assess nutrient intake from food and food plus supplements, nutritional biomarker levels, and school and work absenteeism per year in children and adults. Negative binomial regression models were used to predict mean days of missed work per year and to estimate incidence rate ratios (IRRs) of absenteeism by nutrient biomarker status. Of 7429 children, 77% reported missing school days (mean 4.0 days). Of 8252 adults, 51% reported missing work days (mean 4.9 days). Children and adults who reported more absent days had a significantly lower intake of protein and several essential micronutrients from the diet. When nutrients from supplements were included, this negative association was retained for protein, selenium, choline, and DHA in children and for protein, selenium, vitamin K, choline, potassium, fiber, octadecatrienoic acid, and lycopene in adults. Future studies are needed to ascertain whether dietary interventions, such as access to healthier food options and/or dietary supplements, can reduce absenteeism.

Achieving optimal health is an aspirational goal for the population, yet the definition of health remains unclear. The role of nutrition in health has evolved beyond correcting malnutrition and specific deficiencies and has begun to focus more on achieving and maintaining 'optimal' health through nutrition. As such, the Council for Responsible Nutrition held its October 2022 Science in Session conference to advance this concept. Here, we summarize and discuss the findings of their Optimizing Health through Nutrition - Opportunities and Challenges workshop, including several gaps that need to be addressed to advance progress in the field. Defining and evaluating various indices of optimal health will require overcoming these key gaps. For example, there is a strong need to develop better biomarkers of nutrient status, including more accurate markers of food intake, as well as biomarkers of optimal health that account for maintaining resilience-the ability to recover from or respond to stressors without loss to physical and cognitive performance. In addition, there is a need to identify factors that drive individualized responses to nutrition, including genotype, metabotypes, and the gut microbiome, and to realize the opportunity of precision nutrition for optimal health. This review outlines hallmarks of resilience, provides current examples of nutritional factors to optimize cognitive and performance resilience, and gives an overview of various genetic, metabolic, and microbiome determinants of individualized responses., (Published by Elsevier Inc.)

In the United States, women, while having a longer life expectancy than men, experience a differential risk for chronic diseases and have unique nutritional needs based on physiological and hormonal changes across the life span. However, much of what is known about health is based on research conducted in men. Additional complexity in assessing nutritional needs within gender include the variations in genetics, body compositions, hormonal milieus, underlying chronic diseases, and medication usage, with this list expanding as we consider these variables across the life course. It is clear women experience nutrient shortfalls during key periods of their lives, which may differentially impact their health. Consequently, as we move into the era of precision nutrition, understanding these sex- and gender-based differences may help optimize recommendations and interventions chosen to support health and weight management. Recently, a scientific conference was convened with content experts to explore these topics from a life-course perspective at biological, physiological, and behavioral levels. This publication summarizes the presentations and discussions from the workshop and provides an overview of important nutrition and related lifestyle considerations across the life course. The landscape of addressing female-specific nutritional needs continues to grow; now more than ever, it is essential to increase our understanding of the physiological differences between men and women, and determine how these physiological considerations may aid in optimizing nutritional strategies to support certain personal goals related to health, quality of life, sleep, and exercise performance among women., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To determine associations between serum long-chain (LC) omega-3 fatty acid levels and sleep parameters among adults (N = 1314) in NHANES 2011-2012., Methods: Regression analyses accounting for the complex-survey design were used to assess associations between serum LC omega-3 fatty acid levels, sleep duration, difficulty falling sleeping and sleep disorder., Results: Overall, 48.6% were male, the mean age was 47.2 years, 5% reported very short sleep, 29% short sleep, 63% normal sleep and 3% long sleep. The sum of LC omega-3 fatty acid levels was lower among adults with short versus normal sleep, although differences were attenuated with adjustment for sociodemographic factors. Relative to normal sleep, adults with very short sleep had lower levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and sum of LC omega-3 fatty acids. Differences remained significant (p < .05 for all) with adjustment for sociodemographic factors. No associations were observed with difficulty falling sleeping or sleep disorder., Conclusion: Our results suggest that omega-3 fatty acid levels are associated with healthy sleep duration, although, interventions are needed to clarify causality., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer patients are at risk for malnutrition; the aim of this study was to provide a cost-effectiveness analysis of dietary supplementation in cancer survivors. We estimated prevalence of supplementation, hospitalization rates, quality of life (QOL), cost of care and mortality among cancer survivors. We built a decision analytic model to simulate life-long costs of health care and supplementation and QOL among cancer survivors with and without supplementation. Cost of supplements was derived from national pharmacy databases including single- and multivitamin formularies. One-way and probabilistic sensitivity analysis were performed to evaluate the robustness of the incremental cost-effectiveness ratio (ICER) to changes in supplementation costs and duration. The study cohort represented the national cancer survivor population (average age 61 years, 85% white, 52% male, and 94% insured). Hospitalization rates for supplement users and non-users were 12% and 21%, respectively. The cost of hospitalization was $4030. Supplementation was associated with an additional 0.48 QALYs (10.26 vs. 9.78) at the incremental cost of $2094 ($236,933 vs. $234,839) over the remaining lifetime of survivors (on average 13 years). Adequate nutrition provides a cost-effective strategy to achieving potentially optimum health. Further studies are needed to determine the effects of specific nutrient doses and supplementation on long-term outcomes per cancer type.

Softgel encapsulation is an important manufacturing process used to produce convenient oral dosage forms of pharmaceuticals and dietary supplements. An important step in this process involves the injection of a fill material into a gelatin lined mold, and poor flow of the fill material during the injection may lead to undesired defects. We investigated the effect of fill composition on the injection behavior of an oil-based tricalcium phosphate (TCP) suspension containing lecithin by rheological measurements, capillary breakup extensional rheometry (CaBER), and high-speed flow visualization experiments. Shear rheology for TCP suspensions in soybean oil at concentrations of 27.8 wt% and 55.6 wt% showed shear thinning behaviors both with and without the addition of lecithin. Adding up to 0.5 wt% lecithin led to decreases in shear viscosity, while additions up to 1 wt% caused a slight increase. Results from CaBER and breakoff studies indicated that the length at which flow breakoff occurs was closely related to the Ohnesorge number, a dimensionless parameter representing the relative importance of viscous to surface-tension forces during breakoff, with higher values correlated to longer breakoff lengths. An optimal lecithin concentration exists for minimized TCP suspension viscosity which shortens flow breakoff times and improves softgel capsule seaming quality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Women of childbearing age (WCBA) and women of menopausal age (WMENO) have distinct nutritional needs. Understanding nutrient intake and status in these life stages is critical for tailoring dietary recommendations., Objectives: The objectives of this study were to evaluate total estimated usual nutrient intakes from food and food plus supplements and to compare these to established recommendations for WCBA and WMENO life stages and examine associations between self-reported estimated usual intakes and nutrient status biomarkers., Methods: Twenty-four-hour dietary recall data from 2011-2016 NHANES were used to estimate usual intake of nutrients from food and food plus supplements for WCBA (aged 15-44 y, n = 4,134) and WMENO (aged 40-65 y, n = 3,438). Estimates of mean usual intake were derived and compared across clinically defined nutrient biomarker categories., Results: Both young (aged 15-30 y) and older (aged 31-44 y) WCBA had intakes from food below the Estimated Average Requirement (EAR) for calcium (49% and 44%, respectively), magnesium (62%, 44%), and vitamins A (50%, 44%), C (47%, 46%), D (>97%, >97%), and E (92%, 88%). Similarly, perimenopausal (aged 40-50 y) and menopausal (aged 51-65 y) women had intakes from food below the EAR for calcium (48% and 74%, respectively), magnesium (50%, 49%), and vitamins A (44%, 37%), C (44%, 41%), D (>97%, >97%), and E (88%, 86%). Nutrient gaps decreased with supplement usage. For folate, vitamins D and B-12, and DHA, women in the lowest biomarker category (indicating increased risk of deficiency) had significantly lower intake from food (315.2 ± 25.9 compared with 463.8 ± 5.2 µg dietary folate equivalents, 3.5 ± 0.1 compared with 4.2 ± 0.1 µg, 3.6 ± 0.2 compared with 4.3 ± 0.1 µg, and 0.037 ± 0.005 compared with 0.070 ± 0.006 g, respectively; P < 0.01) of the corresponding nutrient compared with the highest biomarker category., Conclusions: Substantial percentages of WCBA and WMENO are not meeting recommendations for multiple nutrients, whereas supplement usage partially fills nutrient gaps. Dietary intake was positively associated with most nutrient status biomarkers. Specific guidance is needed to ensure adequate nutrient intakes and nutrient status during these critical life stages., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Poverty may be a barrier to acquiring adequate nutrient levels for the prevention of osteoporosis. Age and nutritional intake are major factors that contribute to osteoporosis prevalence. This study examined the relationship between markers of poverty with calcium / vitamin D intake and osteoporosis. A cross-sectional analysis of the United States population was performed using National Health and Nutrition Examination Survey (NHANES) data from 2007-2010 and 2013-2014 for older US adults (n = 3,901 participants, 50 years old and older). Odds of inadequate calcium / vitamin D intake and dietary supplement use and risk of probable osteoporosis were calculated in order to determine the relative difference and possible associations between household income, the Family Monthly Poverty Level Index, food security, and participation in the Supplemental Nutrition Assistance Program (SNAP). A sub-analysis of ethnic disparities and biological sex was also performed. In general, women age 50 and older consistently have inadequate calcium intake, regardless of economic level including poverty. While inadequate calcium intake has a larger prevalence among women, markers of poverty increased the risk of inadequate calcium intake in all men and risk of osteoporosis among some subgroups, with the exception of SNAP program participation. Over one fourth of Non-Hispanic black men in the US are below the poverty line. Approximately half of this population has inadequate calcium (58.9%) and vitamin D (46.7%) intake. Typically, osteoporosis risk is relatively low for Non-Hispanic Black males, however considering poverty status, risk is significantly increased (Relative Risk Ratio [RR]: 2.057 ± 0.012) for those with low income suggesting that calcium and vitamin D supplementation may be of benefit for this population., Competing Interests: KM, LL and SHM are currently salaried employees of Pharmavite LLC. CS is currently a salaried employee of Frost & Sullivan. LT has received compensation as a research consultant from DSM Nutritional Products and the National Cattlemen's Beef Association. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

One third of U.S. adults report short sleep (<7 h), which has been linked to negative health outcomes. Inadequate intake of micronutrients across the U.S. adult population has been reported, and a relationship between sleep conditions and micronutrient intake is emerging. This cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES 2005-2016) ( n = 26,211) showed that participants with short sleep duration had a lower usual intake (Food + Supplements) of calcium, magnesium, and vitamin D in all adults aged 19+ years, and vitamin K in adults aged 19-50 years, even after adjusting for covariates. In addition, participants reporting short sleep had a higher percentage of individuals with intake lower than the estimated average requirement (EAR) across multiple nutrients. Age and gender differences were observed in the prevalence of inadequate intake across multiple nutrients. Adults aged 51-99 years with short sleep duration had inadequate intake with respect to more nutrients. In females there was an association between short sleep and a higher prevalence of inadequate intake (Food + Spp) for calcium, magnesium, and vitamins A, C, D, E, and K (above adequate intake). Conversely, males reporting short sleep only had an inadequate intake of vitamin D. Overall, we demonstrate that short sleep is associated with increased nutrient inadequacy, emphasizing the possible need for dietary supplementation., Competing Interests: Chioma J. Ikonte, Jonathan G. Mun, Carroll A. Reider, Ryan W. Grant, and Susan Hazels Mitmesser are employed at Pharmavite LLC. Victor L. Fulgoni, III is Vice President of Nutrition Impact LLC, which provides database analyses for members of the food and beverage industries.

The aim of this review is to highlight current insights into the roles of choline and docosahexaenoic acid (DHA) in maternal and infant nutrition, with special emphasis on dietary recommendations, gaps in dietary intake, and synergistic implications of both nutrients in infant brain and eye development. Adequate choline and DHA intakes are not being met by the vast majority of US adults, and even more so by women of child-bearing age. Choline and DHA play a significant role in infant brain and eye development, with inadequate intakes leading to visual and neurocognitive deficits. Emerging findings illustrate synergistic interactions between choline and DHA, indicating that insufficient intakes of one or both could have lifelong deleterious impacts on both maternal and infant health.

Background: The 2015–2020 Dietary Guidelines for Americans (DGA) recommend that the general population should consume about 8 ounces (oz.) per week of a variety of seafood, providing approximately 250 mg per day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and that pregnant and lactating women should consume 8&ndash;12 oz. per week of seafood., Methods: We determined the usual intakes, percentage not meeting recommendations, and trends in EPA and DHA intakes among childbearing-age and pregnant women (15&ndash;44 years of age) using the NHANES cycles 2001–2002 through 2013–2014., Results: For the childbearing-age women, the mean usual intake of seafood was 0.44 ± 0.02 oz. equivalent per day and 100% of the population was below the DGA recommendation. Mean usual intakes of EPA, DHA, and combined EPA and DHA from foods and dietary supplements combined were 26.8 ± 1.4, 62.2 ± 1.9, and 88.1 ± 3.0 mg per day, respectively. Over 95% of the sample did not meet the daily intakes of 250 mg EPA and DHA. Similar results were observed for pregnant women. After controlling for covariates, there were slight but significant increases in EPA and DHA intakes from foods and dietary supplements over the 14-year span among childbearing-age ( p = 0.005) and pregnant women ( p = 0.002)., Conclusions: It was estimated that a majority of U.S. childbearing-age and pregnant women consumed significantly lower amounts of seafood than what the DGA recommends, which subsequently leads to low intakes of EPA and DHA; in addition, dietary supplement use has not eliminated the nutrient shortfall.

The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug-nutrient interactions is quite limited. A comprehensive, updated review of the potential drug-nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U.S. adult population is presented. For the majority of the interactions described in this paper, more high-quality intervention trials are needed to better understand their clinical importance and potential consequences. A number of these studies have identified potential risk factors that may make certain populations more susceptible, but guidelines on how to best manage and/or prevent drug-induced nutrient inadequacies are lacking. Although widespread supplementation is not currently recommended, it is important to ensure at-risk patients reach their recommended intakes for vitamins and minerals. In conjunction with an overall healthy diet, appropriate dietary supplementation may be a practical and efficacious way to maintain or improve micronutrient status in patients at risk of deficiencies, such as those taking medications known to compromise nutritional status. The summary evidence presented in this review will help inform future research efforts and, ultimately, guide recommendations for patient care., Competing Interests: Diane L. McKay is a member of the Nature’s Bounty, Co. Scientific Advisory Council. Hua J. Kern is an employee of the Nature’s Bounty, Co. Susan H. Mitmesser was an employee of the Nature’s Bounty Co. when the work was performed.

This review describes effective and ineffective immunonutrition support strategies for the athlete, with a focus on the benefits of carbohydrates and polyphenols as determined from metabolomics-based procedures. Athletes experience regular cycles of physiological stress accompanied by transient inflammation, oxidative stress, and immune perturbations, and there are increasing data indicating that these are sensitive to nutritional influences. The most effective nutritional countermeasures, especially when considered from a metabolomics perspective, include acute and chronic increases in dietary carbohydrate and polyphenols. Carbohydrate supplementation reduces post-exercise stress hormone levels, inflammation, and fatty acid mobilization and oxidation. Ingestion of fruits high in carbohydrates, polyphenols, and metabolites effectively supports performance, with added benefits including enhancement of oxidative and anti-viral capacity through fruit metabolites, and increased plasma levels of gut-derived phenolics. Metabolomics and lipidomics data indicate that intensive and prolonged exercise is associated with extensive lipid mobilization and oxidation, including many components of the linoleic acid conversion pathway and related oxidized derivatives called oxylipins. Many of the oxylipins are elevated with increased adiposity, and although low in resting athletes, rise to high levels during recovery. Future targeted lipidomics-based studies will help discover whether n -3-polyunsaturated fatty acid ( n -3-PUFA) supplementation enhances inflammation resolution in athletes post-exercise., Competing Interests: David C. Nieman is a member of the Nature’s Bounty Co. Scientific Advisory Council, and Susan Hazels Mitmesser is the Director of Nutrition and Scientific Affairs at the Nature’s Bounty Co.

Background: Rapid uptake of vitamin C into blood and retention in tissues are important indicators of the efficacy of vitamin C supplementation and its immune-supporting role. The objective of this study was to evaluate the bioavailability of vitamin C in plasma (reflective of recent intake) and leukocytes (reflective of tissue stores and influences on immune function) from a novel vitamin C formulation, Ester-C(®)., Methods: The study was a double-blind, placebo-controlled, crossover trial. Thirty-six subjects, 18-60 years of age, were randomized to receive placebo (PL, 0 mg vitamin C), ascorbic acid (AA, 1000 mg vitamin C), and Ester-C(®) (EC, 1000 mg vitamin C). Plasma and leukocyte vitamin C were measured baseline and at 2, 4, 8 and 24 h postdose., Results: The concentration and percent change from baseline in plasma were significantly higher with EC at all time points when compared to PL. No significant differences between EC and AA were observed in plasma concentration. Maximum plasma concentration was higher for EC compared to AA (P = 0.039) and PL (P < 0.001). Plasma area under the curve (AUC0-24h) was higher for EC (P < 0.001) compared to PL. The concentration change from baseline in leukocyte vitamin C was increased with EC at 24 h post-dose (P = 0.036) while no significant within-group changes were observed in AA or PL at any time point. The percent change in leukocyte vitamin C concentration was higher for EC at 8 and 24 h compared to AA (P = 0.028 and P = 0.034, respectively) and PL (P = 0.042 and P = 0.036, respectively)., Conclusions: A single dose of EC resulted in favorable percent change in leukocyte vitamin C concentration compared to AA and PL, indicating EC is retained longer within leukocytes. Trial registration ClinicalTrials.gov Identifier NCT01852903.

Soon after birth, the human gastrointestinal tract quickly becomes colonised by a variety of bacterial species. Throughout life the gastrointestinal tract continues to serve as host to a complex society of nonpathological bacteria. Microorganisms, such as probiotics, have the potential to modulate mucosal immune response and reduce gastrointestinal inflammation caused by a variety of infectious and allergic events. The most widely studied genera of probiotics are lactobacilli and bifidobacteria. Lactobacillus rhamnosis strain ATC53103 (LGG) can replenish gut flora during infectious diarrhoeal episodes. This beneficial effect is carried over to traveller's diarrhoea and children experiencing antibiotic-associated diarrhoea. Furthermore, LGG can reduce the risk of respiratory tract infections in children attending daycares and hospitals. With allergic disease on the rise, probiotics have the potential to positively impact atopic dermatitis, asthma, and allergic rhinitis. LGG has been shown to decrease the severity and delay the onset of atopic dermatitis. Additionally, LGG is beneficial in the treatment of allergic colitis and necrotising entercolitis. Some strains of probiotics appear to be useful in the treatment and/or prevention of allergic disease, however, caution must be used when generalising the effectiveness of a specific strain of organism to other organisms and other disease states.

Objective: To investigate the incidence of allergic and respiratory diseases through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy., Study Design: Children who completed randomized, double-blind studies of DHA/ARA-supplemented (0.32%-0.36%/0.64%-0.72% of total fatty acids, respectively) versus nonsupplemented (control) formulas, fed during the first year of life, were eligible. Blinded study nurses reviewed medical charts for upper respiratory infection (URI), wheezing, asthma, bronchiolitis, bronchitis, allergic rhinitis, allergic conjunctivitis, otitis media, sinusitis, atopic dermatitis (AD), and urticaria., Results: From the 2 original cohorts, 89/179 children participated; 38/89 were fed DHA/ARA formula. The DHA/ARA group had significantly lower odds for developing URI (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.08-0.58), wheezing/asthma (OR, 0.32; 95% CI, 0.11-0.97), wheezing/asthma/AD (OR, 0.25; 95% CI, 0.09-0.67), or any allergy (OR, 0.28; 95% CI, 0.10-0.72). The control group had significantly shorter time to first diagnosis of URI (P = .006), wheezing/asthma (P = .03), or any allergy (P = .006)., Conclusions: DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age., (Copyright 2010 Mosby, Inc. All rights reserved.)

Healthy, term infants received extensively hydrolyzed casein formula (EHF; control), the same formula supplemented with Lactobacillus rhamnosus GG (EHF-LGG), or partially hydrolyzed whey:casein (60:40) formula supplemented with LGG (PHF-LGG), in this double-blind, randomized, controlled, parallel, prospective study. Anthropometric measures and 24-hour dietary and tolerance recalls were obtained at 30, 60, 90, 120, and 150 days of age. Blood collected in a subset of infants was analyzed for fatty acid profiles in plasma and red blood cells and for markers of allergic sensitization. Adverse events were recorded throughout the study. Growth rates were not statistically different between EHF and PHF-LGG and between EHF and EHF-LGG from day 14 to day 30, 120, or 150. No relevant differences in formula tolerance, adverse events, or allergic and immune markers were demonstrated between groups. The extensively and partially hydrolyzed formulas supplemented with LGG support normal growth in healthy, term infants and are well tolerated and safe.

Background: Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional. Up to one-half of formula-fed infants experience a formula change during the first six months of life., Methods: The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy, term infants. Infants (335) were randomized to receive either a standard intact cow milk protein formula (INTACT) or a partially hydrolyzed cow milk protein formula (PH) in a 60 day non-inferiority trial. Discontinuance due to study physician-assessed formula intolerance was the primary outcome. Secondary outcomes included number of infants who discontinued for any reason, including parent-assessed., Results: Formula intolerance between groups (INTACT, 12.3% vs. PH, 13.7%) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance. Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants (14.4 vs.11.1%) was significantly different (P = 0.001)., Conclusion: This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy, term infants over a 60-day feeding trial, suggesting nonstandard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants. Parents frequently perceived infant behavior as formula intolerance, paralleling previous reports of unnecessary formula changes., Trial Registration: clinicaltrials.gov: NCT00666120.

Very fussy or extremely fussy infants were randomized to receive: soy-based formula (Soy: n = 82) or a partially hydrolyzed cow's milk protein (CMP), low-lactose formula (PHF: n = 77) in a multicenter, double-blind, randomized, parallel, prospective 28-day feeding trial. Body weight and infant formula tolerance were reported. Adverse events were recorded throughout the study. A significant reduction in mean scores of fussiness, gas, spit-up, and crying compared with baseline measures was observed in infants who received either Soy or PHF within 1 day of formula intake; improvement in symptoms was sustained by study end. Stool consistency remained constant through day 28 in the PHF group, whereas stools in the Soy group became more firm by day 2 and did not return to prestudy consistency. PHF, with a protein profile patterned more closely on human breast milk, improved symptoms of formula intolerance as well as soy-based formula.

Healthy term infants (n = 244) were randomized to receive: (1) control, soy-based formula without supplementation or (2) docosahexaenoic acid-arachidonic acid (DHA + ARA), soy-based formula supplemented with at least 17 mg DHA/100 kcal (from algal oil) and 34 mg ARA/100 kcal (from fungal oil) in a double-blind, parallel group trial to evaluate safety, benefits, and growth from 14 to 120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age and 24-h dietary and tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study. Blood samples were drawn from subsets of 25 infants in each group. Capillary column gas chromatography was used to analyze the percentages of fatty acids in red blood cell (RBC) lipids and plasma phospholipids. Compared with the control group, percentages of fatty acids such as DHA and ARA in total RBC and plasma phospholipids were significantly higher in infants in the DHA + ARA group at 120 days of age (P < 0.001). Growth rates did not differ significantly between feeding groups at any assessed time point. Supplementation did not affect the tolerance of formula or the incidence of adverse events. Feeding healthy term infants soy-based formula supplemented with DHA and ARA from single cell oil sources at concentrations similar to human milk significantly increased circulating levels of DHA and ARA when compared with the control group. Both formulas supported normal growth and were well tolerated.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are two long-chain polyunsaturated fatty acids (LCPUFAs) found naturally in human milk. DHA and ARA have been receiving increased attention from health care professionals and the public. Research suggests that DHA intake and status have a significant impact on visual and cognitive development in breastfed infants. For formula-fed infants, studies have shown mixed results from DHA or DHA plus ARA supplementation. There are several important differences among LCPUFA studies with term infants that may contribute to the differing results, including levels of LCPUFA added to the formula, variations in test methods, ages of infants evaluated, and sources of LCPUFA. Nevertheless, several expert groups recommend that infant formulas be supplemented with DHA and ARA. Recommendations for term infants for DHA and ARA range from 0.2 percent to 0.4 percent and from 0.35 percent to 0.7 percent of the fatty acids, respectively.

Objectives: The present study was designed to evaluate the effect of 2 different combinations of prebiotic ingredients, polydextrose (PDX), galactooligosaccharides (GOS), and lactulose (LOS), at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age., Patients and Methods: Healthy, formula-fed, term infants (n = 226) were randomly assigned to 1 of 3 study formula groups: control group (n = 76), PG4 group (control formula supplemented with 4 g/L of a prebiotic blend, n = 74), or PGL8 group (control formula supplemented with 8 g/L of a prebiotic blend, n = 76). Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age, and 24-hour dietary recall and 24-hour tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study., Results: There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point. Significant differences in stool consistency were detected among the 3 formula groups at 30, 60, and 90 days of age (P < 0.001, P = 0.025, P = 0.004, respectively), with the supplemented formula groups having looser stools than the control group. The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age (P = 0.021 and P = 0.017, respectively), but all of the groups were similar at 60, 90, and 120 days of age. A statistical difference was detected among the formula groups in 3 categories of adverse events: diarrhea (control vs PG4, 4% vs 18%, P = 0.008), eczema (PG4 vs control, 18% vs 7%, P = 0.046; PG4 vs PGL8, 18% vs 4%, P = 0.008), and irritability (control vs PGL8, 4% vs 16%, P = 0.027)., Conclusions: Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula. A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics.

This study was conducted to determine the secretion rate and composition of lipoproteins secreted by HepG2 cells as influenced by the type of fatty acid present in the incubation medium. Cells were preincubated for 24 h with palmitic, oleic, elaidic, linoleic or conjugated linoleic acid (CLA), and the lipoproteins secreted during a subsequent incubation period of 24 h were collected for analysis. The secretion rate of apolipoprotein B-100 (apoB) was significantly greater in HepG2 cells preincubated with elaidic acid compared with those preincubated with palmitic or oleic acid; apoB secretion was greater in cells preincubated with CLA compared with those preincubated with linoleic acid. The lipid composition of secreted lipoproteins was also influenced by fatty acid treatment, resulting in significantly smaller lipoprotein particles secreted by cells preincubated with elaidic acid and CLA compared with those secreted by cells treated with oleic acid and linoleic acid, respectively. Our results are relevant to human metabolism for the following reasons: (1) the size of plasma low-density lipoproteins (LDLs) is determined, at least in part, by the composition of apoB-containing lipoproteins secreted by the liver; (2) small plasma LDL particles are associated with an increased risk of coronary heart disease; and (3) specific dietary fatty acids can affect the composition and size of plasma LDLs, thereby imparting a relative atherogenicity to plasma LDLs independent of LDL cholesterol concentration. The present study therefore suggests that elaidic acid and CLA promote the hepatic secretion of small apoB-containing lipoproteins, which could lead to an increased production of small plasma LDL particles.

The vitamin B-6 intakes and plasma B-6 vitamer levels of healthy nonsupplemented men and women, 19-24 and 25-50 years, were compared. The subjects did not take nutrient supplements or medications or use tobacco products. Subjects were grouped as follows: eight, 19-24 y men; nine, 25-50 y men; 11, 19-24 y women; and 13, 25-50 y women. The estimated vitamin B-6 intakes, obtained via 24-h recalls followed by 2-d food records, of the two groups of men were significantly higher (P < 0.05) than those of the two groups of women. Thirty-five percent of the women reported consuming less than the Estimated Average Requirement for vitamin B-6. The four gender: age groups had similar B-6 vitamer concentrations of plasma pyridoxal-5'-phosphate, 4-pyridoxic acid, pyridoxine, pyridoxamine, and pyridoxamine-5'-phosphate. Males 25-50 y had significantly higher (P < 0.05) plasma pyridoxal concentrations than the two groups of females. All subjects had pyridoxal-5'-phosphate concentrations indicative of vitamin B-6 adequacy. Generally the plasma B-6 vitamer concentrations of these men and women, 19-24 and 25-50 years of age, all having adequate vitamin B-6 status, were similar.